AX+, BX- discrimination learning in the fear-potentiated startle paradigm: possible relevance to inhibitory fear learning in extinction

The neural mechanisms of fear suppression most commonly are studied through the use of extinction, a behavioral procedure in which a feared stimulus (i.e., one previously paired with shock) is nonreinforced repeatedly, leading to a reduction or elimination of the fear response. Although extinction is perhaps the most convenient index of fear inhibition, a great deal of behavioral work suggests that postextinction training conditioned stimuli are both excitatory and inhibitory, making it difficult to determine whether a neural manipulation affects inhibition, excitation, or some combination thereof. For this reason we sought to develop a behavioral procedure that would render a stimulus primarily inhibitory while at the same time avoiding some of the issues raised by the traditional conditioned inhibition paradigm, namely second-order conditioning, external inhibition, and configural learning. Using the fear-potentiated startle paradigm, we adapted an AX+, BX- training procedure in which stimuli A and X were presented simultaneously and paired with shock, and stimuli B and X were presented simultaneously in the absence of shock. In testing, high levels of fear-potentiated startle were seen in the presence of A and AX and much lower levels were seen in the presence of B and AB, as would be predicted if stimulus B were a conditioned inhibitor. We believe this method is a viable alternative to the traditional conditioned inhibition training procedure and will be useful for studying the neural mechanisms of fear inhibition.     

Safety behaviours preserve threat beliefs: Protection from extinction of human fear conditioning by an avoidance response

A laboratory autonomic conditioning procedure was used to establish fear conditioning in human participants by pairing neutral stimuli with electric shock. Participants were also trained to make a button-press response to avoid shock. A target fear stimulus was then extinguished by presenting it without shock. The experimental group was given the opportunity to make the avoidance response during extinction whereas the control group was not. When the fear stimulus was tested without the response available, the control group showed normal extinction of both shock expectancy ratings and skin conductance responses, but the experimental group showed “protection from extinction”: they continued to give high expectancy ratings and strong skin conductance responses. We interpret this effect as analogous to the role of within-situation safety behaviours in preserving threat beliefs during exposure therapy for anxiety disorders. The results support a cognitive account of learning and anxiety. The procedure provides a potential laboratory model for further examination of the cognitive and neural mechanisms underlying anxiety and its reduction.     

Contextual control of the extinction of conditioned fear

Rats received 15 pairings of a CS and shock in one context, and then a series of CS-alone trials in a second context. Even though this extinction procedure produced a complete loss of conditioned suppression, when the animals were returned to the site of original conditioning, suppression was renewed to a level comparable to that of animals that had not undergone extinction. Controls indicated that the renewed suppression was not due solely to pseudoconditioning, suggesting that the CS-US association had survived extinction. Renewed suppression was also demonstrated in a third context that was never associated with shock. Loss of suppression did not necessarily depend upon inhibitory conditioning of the extinction context. The data suggest that extinction of conditioned fear is specific to the context in which it occurs. They also suggest the possibility that animals might discriminate episodes in which a CS is reinforced and nonreinforced independently of the excitatory or inhibitory status of cues, like contextual stimuli, that are coincidentally present during those episodes.     

Excitatory strength of expressive faces: effects of happy and fear expressions and context on the extinction of a conditioned fear response

In a recent study, Orr and Lanzetta (1984) showed that the excitatory properties of fear facial expressions previously described (Lanzetta & Orr, 1981; Orr & Lanzetta, 1980) do not depend on associative mechanisms; even in the absence of reinforcement, fear faces intensify the emotional reaction to a previously conditioned stimulus and disrupt extinction of an acquired fear response. In conjunction with the findings on acquisition, the failure to obtain extinction suggests that fear faces have some of the functional properties of "prepared" (fear-relevant) stimuli. In the present study we compared the magnitude of conditioned fear responses to happy and fear faces when a potent danger signal, the shock electrodes, are attached or unattached. If fear faces are functionally analogous to prepared stimuli, then, even in the absence of veridical support for an expectation of shock, they should retain excitatory strength, whereas happy faces should not. The results are consistent with this view of fear expressions. In the absence of reinforcement, and with shock electrodes removed, conditioned fear responses and basal levels of arousal were of greater magnitude for the fear-face condition than for the happy-face condition.     

The renewal of extinguished conditioned fear with fear-relevant and fear-irrelevant stimuli by a context change after extinction

The acquisition, extinction, and subsequent recovery of conditioned fear can be influenced by the nature of the conditional stimulus (CS) and the context in which the CS is presented. The combined effects of these factors were examined in a differential fear-conditioning procedure with humans. Fear-relevant or fear-irrelevant CSs were followed by a shock unconditional stimulus (US) during acquisition and presented alone during extinction. The CSs were images presented upon different background contexts. Half the participants received the same context during acquisition and extinction and the remaining received different contexts. All participants received test trials in the same context as acquisition. In Experiment 1 (N=64), a renewal of shock expectancy and skin conductance responses was found during test for fear-relevant and fear-irrelevant CSs when extinction was given in a different context. In Experiment 2 (N=72), renewal for fear-relevant stimuli was enhanced when acquisition and test was given in an indoor office context and extinction in an outdoor bush context. The opposite context configuration produced the strongest renewal for fear-irrelevant stimuli. The return of extinguished conditioned fear can occur to fear-relevant stimuli that are commonly associated with clinical fears and its strength may be enhanced when the stimuli are encountered in certain contexts after extinction.     

Mechanisms underlying retarded emergence of conditioned responding following inhibitory training: evidence for the comparator hypothesis

The comparator hypothesis posits that conditioned responding is determined by a comparison at the time of testing between the associative strengths of the conditioned stimulus (CS) and stimuli proximal to the CS at the time of conditioning. The hypothesis treats all associations as being excitatory and treats conditioned inhibition as the behavioral consequence of a CS that is less excitatory than its comparator stimuli. Conditioned lick suppression by rats was used to differentiate four possible sources of retarded responding to an inhibitory CS. These include habituation to the unconditioned stimulus (US), latent inhibition to the CS, blocking of the CS-US association by the conditioning context, and enhanced excitatory associations to the comparator stimuli. Prior research has demonstrated the first three phenomena. Therefore, we employed parameters expected to highlight the fourth one--the comparator process. In Experiment 1, our negative contingency training was shown to produce a conditioned inhibitor that passed inhibitory summation and retardation tests. In Experiment 2 we found transfer of retardation from an inhibitory CS to a novel stimulus when the location where retardation-test training occurred was excitatory, which is indicative of contextual blocking and/or comparator effects. In Experiment 3, extinction of the conditioning context was found to attenuate retardation regardless of whether extinction occurred before or after the CS-US pairings of the retardation test. This indicates that much of the present retardation was due to the comparator process rather than to contextual blocking. Experiment 4 demonstrated that habituation to the US did not contribute to retardation in the present case. Collectively, these studies suggest that retardation following inhibitory training can be explained without recourse to any of the traditional mechanisms of conditioned inhibition.     

Constraints on Pavlovian aversive conditioning: Implications for avoidance learning in the rat

Four experiments investigated the relative degree of control exerted by several conditional stimuli when each stimulus: (a) preceded shock, (b) followed shock, and preceded a shock-free interval, (c) was independent of shock, or (d) was novel. When the onset of an auditory stimulus had preceded shock (Experiments 1, 2A, and 3), it always exerted conditioned excitatory control. When the same stimulus preceded a shock-free interval, it never exerted conditioned inhibitory control. When the onset of light (Experiments 2B, 4), silence (2C), or darkness (1, 2D) preceded a shock-free interval, it always exerted conditioned inhibitory control. However, when one of the latter stimuli preceded shock, it failed to exert excitatory control. Several models of this phenomenon were tested. The implications of these results for the species-specific defence reaction and two-factor theory accounts of avoidance learning were outlined.     

Concurrent excitors limit the extinction of conditioned fear in humans

In a human fear conditioning experiment, with on-line expectancy ratings and electrodermal responding as indices of fear, two neutral stimuli (pictures of geometric shapes) were first established as reliable predictors of an electric shock. In the subsequent extinction phase, the two stimuli were repeatedly presented in compound, without the shock. The final test phase consisted of individual stimulus presentations again, which resulted in a strong return of the conditioned responses. This effect was not observed in non-conditioned control stimuli. Hence, behavioral effects of extinction seem highly specific to the stimulus constellation that has gone through the extinction procedure. We argue that pharmacological, behavioral and/or cognitive manipulations that could prevent configural processing of stimulus constellations have direct clinical potential.     

Transfer of conditioned appetitive stimuli to conditioned aversive excitatory and inhibitory stimuli

The transfer of Pavlovian appetitive stimuli to Pavlovian aversive stimuli was examined in three experiments. In Experiment 1, rats received appetitive (Ap) conditioning designed to establish a flashing-light stimulus as either a CS+, CSo, or CS? for food, or to maintain it as a novel stimulus for US-alone subjects. Then, the stimulus was employed as a signal for weak shock in conditioned-emotional-response (CER) training. Both acquisition and extinction results showed that the ApCS+ facilitated and the ApCS? retarded aversive excitatory conditioning relative to the ApCSo and US-alone controls. Experiment 2 replicated the findings of Experiment 1 with both a moderate and a severe shock in CER training. In Experiment 3, different groups received the same appetitive conditioning as before, but to a flashing-light stimulus which was then employed as a signal for no shock in CER training. The ApCS? facilitated and the ApCS+ retarded aversive inhibitory conditioning relative to ApCSo and US-alone controls. Collectively, these findings establish that, in Pavlovian conditioning, transfer of an appetitive CS to an aversive excitor or inhibitor is facilitated by maintaining the initial conditioning contingency.     

Generalization of excitation and inhibition after different amounts of training of an avoidance baseline

After acquisition of a treadle-pressing response maintained by an avoidance contingency, four groups of pigeons received interdimensional discrimination training. For two groups, the positive stimulus was a 1000-Hertz tone correlated with the avoidance schedule and the negative stimulus was noise correlated with extinction. The discriminative stimuli were reversed for the other two groups. For two groups, the test stimuli were presented during extinction without any shocks during the test stimuli, for the other two groups, an unavoidable shock was presented during each test stimulus. Generalization was measured daily during discrimination training by randomly substituting each of six test frequencies for the 1000-Hertz tone. When the 1000-Hertz tone was correlated with the avoidance schedule, the number of responses to it increased and the excitatory gradient became steeper as a function of the amount of training. When the 1000-Hertz tone was associated with extinction, the number of responses to it decreased as a function of days of training and the inhibitory gradient became slightly steeper, provided that responding to the test stimulus was elevated by unavoidable shock. The training effects parallel those obtained with positive reinforcement.     

Role of conditioned contextual stimuli in reinstatement of extinguished fear

If the unconditioned stimulus (US) is presented independently of the conditioned stimulus (CS) following extinction, the conditioned response may be reinstated to the CS. Three experiments are reported that suggest that reinstatement is mediated by conditioning to contextual stimuli that are present during both US presentation and testing. Shocks presented to rats following the extinction of conditioned suppression reliably reinstated suppression to the CS, but only when they were presented in the context in which testing was later to occur. Reinstatement was also reversed by extinguishing fear to the context through nonreinforced exposure to the context between shock presentation and testing. Reinstatement was obtained in these experiments in spite of procedures that have been used in the past to minimize the influence of context conditioning. Moreover, fear of the context was never detected directly by depressed bar-press rates in the absence of the CS. The results do not support the hypothesis that reinstatement results from an increment in the strength of a memory of the US that has been weakened during extinction. Problems inherent in controlling and detecting levels of context conditioning that may influence behavior toward nominal CSs are discussed.     

Fear Extinction to an Out-Group Face: The Role of Target Gender

ABSTRACT— Conditioning studies on humans and other primates show that fear responses acquired toward danger-relevant stimuli, such as snakes, resist extinction, whereas responses toward danger-irrelevant stimuli, such as birds, are more readily extinguished. Similar evolved biases may extend to human groups, as recent research demonstrates that a conditioned fear response to faces of persons of a social out-group resists extinction, whereas fear toward a social in-group is more readily extinguished. Here, we provide an important extension to previous work by demonstrating that this fear-extinction bias occurs solely when the exemplars are male. These results underscore the importance of considering how gender of the target stimulus affects psychological and physiological responses to out-group threat.     

A randomized controlled trial of the effect of D-cycloserine on extinction and fear conditioning in humans

Previous research has shown that D-cycloserine (DCS) facilitates extinction of Pavlovian fear conditioning in rats and enhances exposure therapy in humans. The aim of this study was to test the effect of DCS on extinction of fear conditioning in humans. In three experiments, 238 participants were given either DCS (50 or 500 mg) or placebo 2-3 h before extinction training following a differential shock conditioning paradigm. Clear extinction and recovery (return of fear) effects were observed on both skin conductance and self-reported shock expectancy measures in three studies. DCS had no influence on these effects. The same pattern was observed when the analysis was restricted to aware participants or to good conditioners, when fear-relevant cues (pictures of snakes) were used as the conditioned stimuli, or when analysis was restricted to heightened snake-fearful participants. These results suggest that DCS may not enhance the extinction, or prevent the recovery, of learned fear in a differential Pavlovian conditioning paradigm in humans. Further experimental research is needed to better understand the mechanisms underlying the therapeutic effects of DCS.     

Extinguishing conditioned inhibition in flavour-aversion learning: Effects of repeated testing and extinction of the excitatory element

Three conditioned inhibition experiments using an A+/AX- design are reported in which lithium-mediated excitatory conditioning occurred to distinctive environmental stimuli and inhibitory conditioning to a vinegar flavour. Increased vinegar preferences were observed (i.e., conditioned inhibition) in each experiment, and these preferences extinguished with repeated testing as well as following extinction of the excitatory element. Vinegar preferences could be reinstated through reconditioning of the extinguished excitatory stimulus. These experiments speak to the status of inhibitory responding as a “slave” process to conditioned excitation.     

Temporally massed CS presentations generate more fear extinction than spaced presentations

Rodent fear conditioning models both excitatory learning and the pathogenesis of human anxiety, whereas extinction of conditional fear is a paradigm of inhibitory learning and the explicit model for behavior therapy. Many studies support a general learning rule for acquisition: Temporally spaced training is more effective than massed training. The authors asked whether this rule applies to extinction of conditional fear in mice. The authors find that both short- and long-term fear extinction are greater with temporally massed presentations of the conditional stimulus (CS). The data also indicate that once CS presentations are sufficiently massed to initiate, or "induce," extinction learning, further CS presentations are more effective when spaced.     

Predictability and controllability: Differential effects upon contextual fear

The independence of action of controllability and predictability has recently been questioned by research demonstrating that the effects of control over shock termination can be mimicked by feedback stimuli when a contextual fear measure is used. This suggests that the varied effects of controllability, particularly controllability of shock termination, may result not from controllability per se but from predictability of shock absence. The present experiments address this issue by examining whether controllability and predictability similarly affect contextual fear under several parametric conditions. In Experiment 1, control over shock termination was found to reduce contextual fear at an earlier point in training than prediction of shock absence. Experiment 2 demonstrated an effect of controllability under conditions in which the feedback effect is precluded. Experiment 3 examined the possibility that the group differences observed in the above experiments could be due to a potential difference in the conditionability of the response-produced stimulation and the external feedback stimulus. The outcome of this study makes it unlikely that this is the case, since no evidence of overshadowing of the feedback stimulus was observed on a test of its associative strength. These experiments suggest that the effects of controllability may not be reducible to those of predictability. Furthermore, they have important implications for theoretical proposals concerning the effect of feedback on contextual fear.     

Blockade of GABAA receptors in the interpositus nucleus modulates expression of conditioned excitation but not conditioned inhibition of the eyeblink response

The cerebellum and related brainstem structures are essential for excitatory eyeblink conditioning. Recent evidence indicates that the cerebellar interpositus and lateral pontine nuclei may also play critical roles in conditioned inhibition (CI) of the eyeblink response. The current study examined the role of GABAergic inhibition of the interpositus nucleus in retention of CI. Male Long-Evans rats were implanted with a cannula positioned just above or in the anterior interpositus nucleus before training. The rats were trained with two different tones and a light as conditioned stimuli, and a periorbital shock as the unconditioned stimulus. CI training consisted of four phases: 1) excitatory conditioning (8 kHz tone paired with shock); 2) feature-negative discrimination (2 kHz tone paired with shock or 2 kHz tone concurrent with light); 3) summation test (8 kHz tone or 8 kHz tone concurrent with light); and 4) retardation test (light paired with shock) After reaching a criterion level of performance on the feature-negative discrimination (40% discrimination), 0.5 μl picrotoxin (a GABA_A receptor antagonist) was infused at one of four concentrations, each concentration infused during separte test sessions. Picrotoxin transiently impaired conditioned responses during trials with the excitatory stimulus (tone) in a dose-dependent manner, but did not significantly impact responding to the inhibitory compound stimulus (tone-light). The results suggest that expression of conditioned inhibition of the eyeblink conditioned response does not require GABAergic inhibition of neurons in the anterior interpositus nucleus.     

Blockade of GABAA Receptors in the Interpositus Nucleus Modulates Expression of Conditioned Excitation but not Conditioned Inhibition of the Eyeblink Response

The cerebellum and related brainstem structures are essential for excitatory eyeblink conditioning. Recent evidence indicates that the cerebellar interpositus and lateral pontine nuclei may also play critical roles in conditioned inhibition (CI) of the eyeblink response. The current study examined the role of GABAergic inhibition of the interpositus nucleus in retention of CI. Male Long-Evans rats were implanted with a cannula positioned just above or in the anterior interpositus nucleus before training. The rats were trained with two different tones and a light as conditioned stimuli, and a periorbital shock as the unconditioned stimulus. CI training consisted of four phases: 1) excitatory conditioning (8 kHz tone paired with shock); 2) feature-negative discrimination (2 kHz tone paired with shock or 2 kHz tone concurrent with light); 3) summation test (8 kHz tone or 8 kHz tone concurrent with light); and 4) retardation test (light paired with shock). After reaching a criterion level of performance on the feature-negative discrimination (40% discrimination), 0.5 microl picrotoxin (a GABAA receptor antagonist) was infused at one of four concentrations, each concentration infused during separate test sessions. Picrotoxin transiently impaired conditioned responses during trials with the excitatory stimulus (tone) in a dose-dependent manner, but did not significantly impact responding to the inhibitory compound stimulus (tone-light). The results suggest that expression of conditioned inhibition of the eyeblink conditioned response does not require GABAergic inhibition of neurons in the anterior interpositus nucleus.     

Extinction of an emotional response in the presence of facial expressions of emotion

Previous studies (Lanzetta & Orr, 1980, 1981; Orr & Lanzetta, 1980) have demonstrated that fear facial expressions have the functional properties of conditioned excitatory stimuli, while happy expressions behave as conditioned inhibitors of emotional responses. The present study uses a summation conditioning procedure to distinguish between associative and nonassociative (selective sensitizations, attentional) interpretations of these findings. A neutral tone was first established as a conditioned excitatory CS by reinforcing tone presentations with shock. In subsequent nonreinforced test trials the excitatory tone was paired with either fear, happy, or neutral facial expressions. A tone alone and a tone/nonface slide compound were used as controls. The results indicate that phasic and tonic skin conductance responses to the tone/fear expression compound were significantly larger during extinction than for all other experimental and control groups. No significant differences were found among these latter conditions. The findings support the assumption that the excitatory characteristics of fear expressions do not depend on associative mechanisms. In the presence of fear cues, fear facial expressions intensify the emotional reaction and disrupt extinction of a previously acquired fear response. Happy facial expressions however, do not function as conditioned inhibitors in the absence of reinforcement, suggesting that the previously found inhibition was associative in nature.This research was supported by NSF grant No. 77-08926 and by funds from the Lincoln Filene Endowment to Dartmouth College.     

Associative learning versus fear habituation as predictors of long-term extinction retention

Violation of unconditioned stimulus (US) expectancy during extinction training may enhance associative learning and result in improved long-term extinction retention compared to within-session habituation. This experiment examines variation in US expectancy (i.e., expectancy violation) as a predictor of long-term extinction retention. It also examines within-session habituation of fear-potentiated startle (electromyography, EMG) and fear of conditioned stimuli (CS) throughout extinction training as predictors of extinction retention. Participants (n?=?63) underwent fear conditioning, extinction and retention and provided continuous ratings of US expectancy and EMG, as well as CS fear ratings before and after each phase. Variation in US expectancy throughout extinction and habituation of EMG and fear was entered into a regression as predictors of retention and reinstatement of levels of expectancy and fear. Greater variation in US expectancy throughout extinction training was significantly predictive of enhanced extinction performance measured at retention test, although not after reinstatement test. Slope of EMG and CS fear during extinction did not predict retention of extinction. Within-session habituation of EMG and self-reported fear is not sufficient for long-term retention of extinction learning, and models emphasizing expectation violation may result in enhanced outcomes.